Methylene Blue: COVID-19 and Lung Disease

Table of Contents

1. Why Researchers Tried It: Proposed Mechanisms
2. Randomised Trials in People
3. The Registration Question
4. A Different Use: Methylene Blue-Treated Plasma
5. Case Series and Observational Reports
6. Light-Activated Methylene Blue in the Nose and Mouth
7. Septic Shock and Vasoplegia: The Established Critical-Care Use
8. Laboratory Studies in Cells and Computer Models
9. Animal Studies of Lung Injury and Infection
10. What Is Not Known
11. Safety Findings That Matter in This Setting
12. Key Research Papers
13. Connections

Why Researchers Tried It: Proposed Mechanisms

None of the ideas below has been shown to explain a benefit in patients. They are the reasons researchers gave for testing Methylene Blue, and they are labelled here as proposed mechanisms.

• Nitric oxide and guanylate cyclase. In sepsis, nitric oxide relaxes blood vessels by switching on the enzyme guanylate cyclase and its messenger molecule, cyclic guanosine monophosphate. A 2020 review describes Methylene Blue as blunting this pathway, which is the basis of its use in shock with dangerously low blood pressure (Saha 2020). In a 2020 report from an Iranian intensive care unit, nitrite and nitrate (breakdown products of nitric oxide), methemoglobin and markers of oxidative stress were all significantly higher in 25 critically ill COVID-19 patients than in 25 healthy people; the authors proposed that nitric oxide and oxidative stress drive a self-reinforcing inflammatory cycle in critical COVID-19 (Alamdari 2020).
• Reactive oxygen and nitrogen species. A 2021 hypothesis paper argued that drugs aimed at the virus or at one or two inflammatory signalling proteins arrive too late in severe COVID-19, and that the excess of reactive oxygen and nitrogen species is left untreated. The authors proposed testing Methylene Blue in COVID-related acute respiratory distress syndrome and, in particular, early in infection (Scigliano 2021). This was a proposal, not a study.
• Methemoglobin and oxygen carriage. A 2021 review of how blood carries oxygen in COVID-19 suggested that methemoglobin (a form of hemoglobin that cannot carry oxygen) forms in the illness, and listed Methylene Blue, which converts methemoglobin back to working hemoglobin, among the treatments under discussion (Böning 2021).
• Mitochondria. In cell and animal studies, Methylene Blue can pass electrons along the mitochondrial energy chain when parts of it are blocked. That mechanism is described on the Mitochondrial Mechanism and Bioenergetics page; no study on this page measured mitochondrial function in COVID-19 patients.
• Direct action on the virus. In cells, Methylene Blue inactivates SARS-CoV-2 particles and reduces infection at low micromolar concentrations, with and without light (see Laboratory Studies). Whether those concentrations act inside the human lung is a separate question that the cell work cannot answer.

Two reviews from 2021 and 2024 gather these arguments and the early clinical reports in one place (Dabholkar 2021; Emadi 2024). The 2024 review comes from the same Iranian research group that ran the trials described below, and it concludes in favour of the drug; it is a narrative review, not a systematic one.

Back to Table of Contents

Randomised Trials in People

Randomised trials are the strongest kind of study on this page, but both trials of Methylene Blue itself in COVID-19 lung disease were small, run at hospitals in Iran, and open-label: patients and staff knew who received the drug, and the comparison group received no placebo.

The Iran Phase 2 trial (2021)

• Design: randomised, controlled, open-label Phase 2 trial in an academic medical centre. 80 hospitalised patients with severe COVID-19 were assigned to oral Methylene Blue (in its reduced form) plus standard care (40 patients) or standard care alone (40 patients). The abstract does not state the dose.
• Primary outcomes: oxygen saturation and breathing rate on days 3 and 5. Secondary outcomes: hospital stay and death within 28 days.
• Results reported: in the Methylene Blue group, oxygen saturation and breathing rate improved significantly on day 3 and day 5. In the standard-care group they did not improve significantly on day 3 but did on day 5. The hospital stay was significantly shorter in the Methylene Blue group. Deaths were 12.5% (Methylene Blue) and 22.5% (standard care), that is, 5 and 9 of 40 patients; the abstract gives no statistical test for the death difference.
• The authors’ conclusion: adding Methylene Blue improved oxygen saturation and breathing, which they state resulted in a shorter hospital stay and fewer deaths (Hamidi-Alamdari 2021).

The acute respiratory distress syndrome trial (2025)

• Design: randomised clinical trial in 122 hospitalised patients with acute respiratory distress syndrome from COVID-19: 62 received oral Methylene Blue with standard treatment and 60 received standard treatment alone. The abstract does not state the dose or describe any blinding. It was registered in the Iranian Registry of Clinical Trials.
• Oxygen saturation: rose more over time in the Methylene Blue group (difference between groups P = 0.022; time-by-group interaction P = 0.019), with an increase of 6.42% in that group.
• C-reactive protein (an inflammation marker): fell over time in both groups, with no significant difference between groups (P = 0.092), though the pattern of decrease differed (interaction P = 0.019). At discharge, oxygen saturation and an illness-severity score had improved more in the Methylene Blue group.
• Survival and hospital stay: the length of hospital stay and death rates at one and three months did not differ significantly between the groups.
• The authors’ conclusion: oral Methylene Blue improved oxygen saturation and reduced inflammatory markers, but had no significant effect on survival or length of hospital stay (Sanei 2025).

Read together: both trials report better oxygen saturation with Methylene Blue. The larger and later trial found no difference in survival or hospital stay. Neither trial was blinded, and oxygen saturation is a measurement that can move without changing whether a patient lives.

Back to Table of Contents

The Registration Question

The 2021 Phase 2 trial gives the ClinicalTrials.gov number NCT04370288. So does the earlier 2020 report of five critically ill patients (Alamdari 2020). The ClinicalTrials.gov record itself, read for this page, describes something different from the published trial:

• Title: “The Clinical Trial of Application of Methylene Blue Vial for Treatment of Covid-19 Patients”; listed as Phase 1, with an estimated enrolment of 20.
• Intervention: a mixture of Methylene Blue, vitamin C and N-acetyl cysteine that “will be injected” into patients.
• Primary outcome: the proportion of patients remaining free of the need for mechanical ventilation at day 7. Oxygenation (as a blood-gas ratio at day 2), death at day 28 and hospital stay were secondary outcomes.
• The record was last updated in April 2020, and its status is listed as unknown.

The published trial instead gave the drug by mouth to 80 patients and named oxygen saturation and breathing rate as its primary outcomes. McMaster University’s COVID-19 Evidence Alerts service, which had clinicians rate new papers, carried rater comments on this trial (the service closed in 2025; an archived copy from June 2021 was read for this page). A hospital-medicine rater wrote that the registry entry says the formulation would be given intravenously with intubation as the primary outcome, that intubation is not reported in the paper, and that oxygen saturation on room air became the primary outcome instead. An infectious-disease rater called the work interesting but preliminary, with possible biases and analysis problems, and wrote that the sample size and outcomes limit any clinically useful conclusion. Other raters called the results encouraging or promising and wrote that they need confirmation in a larger, properly designed trial.

A change of primary outcome between registration and publication is one of the things evidence reviewers look for, because it can make a trial look more positive than its original plan would have.

Back to Table of Contents

A Different Use: Methylene Blue-Treated Plasma

The largest and best-designed randomised trial in the COVID-19 Methylene Blue literature did not test Methylene Blue as a medicine. Blood banks in several countries treat donated plasma with Methylene Blue and light to inactivate viruses. In this trial the plasma came from people who had recovered from COVID-19, and the question was whether that plasma helped.

• Outpatient trial (2022): multicentre, double-blind, placebo-controlled trial in Catalonia, Spain, in 376 adults aged 50 or over with mild COVID-19 of 7 days or less. One intravenous infusion of high-antibody Methylene Blue-treated convalescent plasma did not reduce hospital admission within 28 days (12% versus 11% with saline) and did not reduce viral load by day 7. The trial was stopped early because most of the target population had been vaccinated (Alemany 2022).
• Inpatient sub-study (2023): among 175 people in hospital with SARS-CoV-2 pneumonia who received one unit of convalescent plasma, worsening of breathing occurred in 5 of 90 (5.6%) who received Methylene Blue-treated plasma and 9 of 85 (10.6%) who received plasma treated by other methods (P = 0.220). The authors concluded that Methylene Blue pathogen reduction did not make the plasma less effective (Romera Martínez 2023).

These studies are about plasma processing. They say nothing about whether Methylene Blue given to a patient treats COVID-19.

Back to Table of Contents

Case Series and Observational Reports

Every report in this section describes patients who received Methylene Blue without a randomised comparison group. Without one, there is no way to tell how many of these patients would have improved, or died, on standard care alone.

Intravenous rescue series, India (2021)

50 patients with low-oxygen COVID-19 at one tertiary hospital (June to September 2020) received intravenous Methylene Blue as rescue therapy when their oxygen needs were high, alongside standard care. The case series gave 1 milligram per kilogram of body weight, up to five doses, after checking glucose-6-phosphate dehydrogenase levels. The median ratio of oxygen saturation to inspired oxygen rose from 132.5 before dosing to 284 before the final outcome. Six patients needed invasive mechanical ventilation; 30 were discharged (60%) and 20 died. The authors reported no major side effects (Mahale 2021). Size: 50. Control group: none.

Nebulised, humidifier and intravenous use, India (2022)

Published in a journal not indexed in PubMed (MGM Journal of Medical Sciences); the article was opened and read for this page. A prospective single-centre study of 103 hospitalised patients with moderate and severe acute respiratory distress syndrome from COVID-19 (June 2020 to July 2021) described three routes used together: nebulised Methylene Blue (0.5 millilitres of a 0.5% solution in 2.5 millilitres of distilled water) three times a day; a 10-millilitre ampoule in 90 millilitres of water through the oxygen humidifier port while oxygen was needed; and 2 milligrams per kilogram given intravenously over 3 hours once a day for 5 days. People with glucose-6-phosphate dehydrogenase deficiency, people taking antidepressants or other serotonergic medicines, pregnant and breastfeeding patients, and those with severely reduced kidney function were excluded. The authors report that oxygen saturation improved by 7.827%, that ferritin, C-reactive protein, lactate dehydrogenase and D-dimer fell after treatment, that 86.4% recovered and were discharged, and that all-cause mortality was 13.59%. They list the single-centre design among its limitations (Ghodke 2022). Size: 103. Control group: none described.

Humidifier case report (2022)

A 51-year-old man arrived with an oxygen saturation of 70% on room air and was treated with noninvasive ventilation and standard care. Because low oxygen and breathing distress persisted, Methylene Blue was given through the humidifier for 5 days; the authors report a significant fall in breathing distress and a steep rise in oxygen saturation (Yella 2022). Size: 1 patient.

Five critically ill patients, Iran (2020)

In the same report that measured nitric oxide products, five intensive-care COVID-19 patients were given a Methylene Blue, vitamin C and N-acetyl cysteine combination as a last therapeutic option; four of the five were described as responding well (Alamdari 2020). The report is titled a Phase 1 trial. Size: 5. Control group: none.

Letters and hypotheses

Several letters and hypothesis papers from 2020 and 2021 proposed Methylene Blue for COVID-19 (for example Scigliano 2021). They contain no patient data and are not evidence that the drug works.

Back to Table of Contents

Light-Activated Methylene Blue in the Nose and Mouth

A separate line of work applied Methylene Blue to the nose and mouth and switched it on with red light, a technique called photodynamic disinfection. This works on the virus at the surface; it is not a treatment of the lungs.

• Nasal photodynamic disinfection (2022): in cells, the method reduced human coronavirus OC43 and SARS-CoV-2 by up to 6 logs (a millionfold). In a proof-of-principle clinical study, viral infectivity in nasal swabs fell in 90% of samples and was undetectable in 70%. Viral genetic material counts by polymerase chain reaction varied, which the authors attribute to the light treatment breaking the viral genetic material into fragments (Pires 2022).
• Pilot study, Bahamas (2022): eight people with COVID-19 during the Delta wave received light-activated Methylene Blue in the nose and mouth, with oral Methylene Blue and/or red-light therapy added according to need. The authors report rapid falls in viral load, negative tests within a median of 4 days, no significant adverse effects and no hospital admissions among those who completed the protocol. They state that extensive studies in a large group are needed to confirm the results (Hepburn 2022). Size: 8. Control group: none.

Back to Table of Contents

Septic Shock and Vasoplegia: The Established Critical-Care Use

In intensive care medicine, Methylene Blue already has a recognised use outside COVID-19: as an intravenous add-on in shock where blood vessels have lost their tone (vasoplegia), typically in septic shock or after heart surgery. This evidence is often cited in COVID-19 discussions, so it helps to see how it differs.

• Pilot randomised trial (2001): 20 patients with septic shock; 10 received intravenous Methylene Blue and 10 saline. Methylene Blue raised blood pressure, kept oxygen delivery steady and reduced the need for adrenaline-type drugs. Five patients given Methylene Blue survived, compared with three in the control group (Kirov 2001).
• Randomised trial (2023): 91 patients with septic shock received Methylene Blue or placebo within 24 hours. The Methylene Blue group came off blood-pressure drugs sooner (69 versus 94 hours) and left intensive care 1.5 days and hospital 2.7 days earlier. Days on a ventilator and deaths were similar between the groups (Ibarra-Estrada 2023).
• Meta-analysis (2024): six randomised trials, 302 patients with septic shock. Methylene Blue may reduce short-term death (risk ratio 0.66), hospital stay and time on blood-pressure drugs, all rated low-certainty evidence; no difference in adverse events was found (Fernando 2024).
• Meta-analysis of all non-adrenaline blood-pressure drugs (2024): across 51 trials, the group as a whole was associated with lower mortality in septic shock, but no single drug — Methylene Blue included — showed a significant survival benefit on its own (Kotani 2024).

How this differs from the COVID-19 work: the shock trials give the drug intravenously to treat dangerously low blood pressure, the 2023 trial used a placebo, and the outcomes are blood pressure and drug requirements. The COVID-19 trials gave the drug by mouth, without a placebo, and measured oxygen saturation. A finding in one setting does not carry over to the other.

Back to Table of Contents

Laboratory Studies in Cells and Computer Models

Every result in this section was obtained in cells in a dish or in a computer model, not in people.

• SARS-CoV-2 and H1N1 influenza, in cells (2021): Methylene Blue destroyed H1N1 influenza virus and SARS-CoV-2 at low micromolar concentrations in cell culture, both before and after cells were infected, and without ultraviolet activation; genetic material was broken down more with light and with longer exposure (Cagno 2021).
• SARS-CoV-2 replication, in cells (2020 and 2021): without light, Methylene Blue inhibited SARS-CoV-2 in monkey kidney cells at a median effective concentration of 0.30 micromolar (Gendrot 2020). A follow-up in the same cells found activity at both virus-entry and post-entry stages; combinations with some antimalarial drugs were additive, while combinations with others and with remdesivir were antagonistic (Gendrot 2021).
• Light-activated inactivation, in cells (2021 and 2022): Methylene Blue with red laser light inactivated SARS-CoV-2 suspensions and protected cells from infection; it also had antiviral activity without light (Svyatchenko 2021). One minute of light-activated treatment of samples taken from COVID-19 patients reduced the virus’s signal by 99.99% (Lobo 2022).
• Human airway tissue, in culture (2022): Methylene Blue given after exposure blocked infection of cultured human nasal and bronchial airway tissue by the Omicron BA.1 variant (Volle 2022).
• Blocking the virus’s attachment, in a protein assay and in cells (2020): Methylene Blue inhibited the binding of the virus’s spike protein to the angiotensin-converting enzyme 2 receptor at a half-maximal concentration of 3 micromolar, and blocked entry of a spike-carrying test virus into cells at a similar concentration (Bojadzic 2020).
• Molecular modelling, in a computer simulation (2023): a Brownian-dynamics simulation identified binding sites for Methylene Blue on the SARS-CoV-2 envelope, including the spike and envelope proteins and negatively charged lipids (Kovalenko 2023).

A 2024 study is the main caution here. Methylene Blue strongly destroyed a SARS-CoV-2-related pangolin coronavirus outside cells, but did not inhibit its replication inside cells, and showed no noticeable antiviral effect in a lethal infection model in mice engineered to carry the human receptor. Mouse plasma made the compound less active (Wei 2024). Strong activity in a dish did not translate into an effect in a living animal.

Back to Table of Contents

Animal Studies of Lung Injury and Infection

Rat studies of acute lung injury from causes other than COVID-19 are often cited as support. Each result below is in rats.

• Paraquat poisoning, in rats (2013): Methylene Blue given 2 hours after the weedkiller paraquat raised the antioxidant enzyme superoxide dismutase, reduced lung fluid and markers of damage, and reduced tissue injury in rats (Tian 2013).
• Oleic-acid lung injury, in rats (2016): in rats, improvements in lung fluid and leak of protein were not statistically significant; the lung tissue showed smaller damaged areas under the microscope, whether Methylene Blue was given before or after the injury (Cassiano Silveira 2016).
• Lung injury after limb ischemia, in rats (2018): after blood flow to a hind limb was stopped and restored, Methylene Blue reduced oxidative-stress markers, the inflammatory signals interleukin-1 beta and interleukin-6, and lung swelling in rats (Wang 2018).
• Lung injury after cardiac surgery-style circulatory arrest, in rats (2025): intravenous Methylene Blue before cooled circulatory arrest improved blood gases and reduced lung damage, inflammatory signals and a form of inflammatory cell death in lung immune cells in rats (Ding 2025).
• Coronavirus infection, in mice (2024): as noted above, no noticeable antiviral effect in mice infected with a SARS-CoV-2-related coronavirus (Wei 2024).

Back to Table of Contents

What Is Not Known

• No large multicentre trial. No large, multicentre, placebo-controlled trial of Methylene Blue as a treatment for COVID-19 or acute respiratory distress syndrome was found in PubMed for this page. The two randomised trials enrolled 80 and 122 patients in Iran.
• No shown effect on deaths. The larger randomised trial found no significant difference in survival or hospital stay (Sanei 2025). The smaller trial reported fewer deaths without a statistical test in its abstract, and its published outcomes differ from its registered ones.
• Open-label designs. In both trials everyone knew who received the drug, which can influence care decisions and measurements.
• Oxygen saturation as the main outcome. A better oxygen saturation reading is not the same as surviving or leaving hospital sooner. The trial abstracts do not say how oxygen saturation was measured, which matters because of the pulse oximetry interference described below.
• Unknown dose and route. Studies used oral, intravenous, nebulised and humidifier routes, often several at once, at different doses. Which, if any, matters is unknown.
• From dish to patient. Strong virus-killing activity in cells did not produce an antiviral effect in infected mice (Wei 2024).
• No regulatory approval for COVID-19. The US label lists acquired methemoglobinemia as the only indication (US label, 2023).

Two COVID-era papers on Methylene Blue were later retracted — a 2021 study of plasma virus inactivation and a 2022 letter on clinical use — and neither is used on this page.

Back to Table of Contents

Safety Findings That Matter in This Setting

Seriously ill COVID-19 patients are often taking several medicines, may have low oxygen already, and are monitored mainly with pulse oximeters. The safety findings below are documented in the US label, the 2011 drug safety communication and the medical literature. More detail is on the Drug Interactions and Serotonin Syndrome and Methemoglobinemia and Glucose-6-Phosphate Dehydrogenase Deficiency pages.

Serotonin syndrome with antidepressants

On July 26, 2011, the US Food and Drug Administration announced that it had received reports of serious central nervous system reactions when Methylene Blue was given to patients taking psychiatric medicines that work through serotonin. It described Methylene Blue as a potent, reversible monoamine oxidase inhibitor, and stated that it was generally not to be given to patients taking serotonergic drugs (US Food and Drug Administration, July 2011). The current US label carries a boxed warning that Methylene Blue may cause serious or fatal serotonin syndrome when used with serotonergic drugs and opioids, naming selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and monoamine oxidase inhibitors (US label, 2023). The Indian 103-patient study excluded people taking antidepressants and serotonergic medicines for this reason (Ghodke 2022).

Hemolysis in glucose-6-phosphate dehydrogenase deficiency

The label contraindicates Methylene Blue in glucose-6-phosphate dehydrogenase deficiency and states that treating these patients may result in severe hemolysis (destruction of red blood cells) and severe anemia (US label, 2023). An evidence-based review found solid evidence for only seven medicines causing hemolysis in this deficiency, and Methylene Blue was one of them (Youngster 2010). COVID-19 adds a complication: case reports describe COVID-19 itself setting off both hemolysis and methemoglobinemia in people with the deficiency who had taken no oxidising drug, and their authors note that giving Methylene Blue in this situation can worsen hemolysis (Malakah 2023; Kashari 2022). The intravenous case series checked enzyme levels before dosing, and the 103-patient study excluded people with the deficiency (Mahale 2021; Ghodke 2022).

The methemoglobin paradox and breathing effects at higher doses

Methylene Blue treats methemoglobinemia, yet the label records that large cumulative intravenous doses (7 milligrams per kilogram or more) caused, among other effects, shortness of breath, rapid breathing, chest tightness and mild methemoglobinemia (up to 7%). It also records that hypotension, wheezing and reduced oxygenation have been reported after single doses of 3 milligrams per kilogram or more, and that a single dose of 20 milligrams per kilogram or more caused severe hemolysis and death (US label, 2023). A review describes this two-sided behaviour as coming partly from the drug’s oxidising action, the same mechanism that causes methemoglobinemia (Pushparajah Mak 2021).

Interference with pulse oximetry

The label states that Methylene Blue in the blood may cause pulse oximetry to underestimate oxygen saturation, and describes taking an arterial blood sample and testing it by another method when a saturation measurement is needed during or shortly after an infusion (US label, 2023). In a lung-disease setting, where oxygen saturation is both the main monitoring tool and the main trial outcome, this is a measurement problem as well as a safety one.

Decisions about medicines in hospital belong with the treating clinicians.

Back to Table of Contents

Key Research Papers

1. Hamidi-Alamdari D, Hafizi-Lotfabadi S, Bagheri-Moghaddam A, et al. METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2. Revista de investigacion clinica. 2021;73(3):190-198. PubMed PMID: 34019535
2. Sanei ZS, Shahrahmani F, Khaleghi Manesh B, et al. Methylene blue for COVID-19 ARDS: insights from a randomized Clinical Trial. Naunyn-Schmiedeberg’s archives of pharmacology. 2025;398(2):1915-1924. PubMed PMID: 39207597
3. Alamdari DH, Moghaddam AB, Amini S, et al. Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. European journal of pharmacology. 2020;885:173494. PubMed PMID: 32828741
4. Mahale N, Godavarthy P, Marreddy S, et al. Intravenous Methylene Blue as a Rescue Therapy in the Management of Refractory Hypoxia in COVID-19 ARDS Patients: A Case Series. Indian journal of critical care medicine. 2021;25(8):934-938. PubMed PMID: 34733037
5. Yella SHT, Yella SST, Sasanka KSBSK, et al. Does Methylene Blue Satisfy an Option in COVID-19 ARDS. Infectious disorders drug targets. 2022;22(6):e170322202339. PubMed PMID: 35301956
6. Alemany A, Millat-Martinez P, Corbacho-Monné M, et al. High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial. The Lancet. Respiratory medicine. 2022;10(3):278-288. PubMed PMID: 35150610
7. Romera Martínez I, Bueno Cabrera JL, Domingo-Morera JM, et al. Pathogen reduction with methylene blue does not have an impact on the clinical effectiveness of COVID-19 convalescent plasma. Vox sanguinis. 2023;118(4):296-300. PubMed PMID: 36734378
8. Hepburn J, Williams-Lockhart S, Bensadoun RJ, et al. A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up. Antioxidants (Basel). 2022;11(11):2211. PubMed PMID: 36358582
9. Pires L, Wilson BC, Bremner R, et al. Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2. Scientific reports. 2022;12(1):14438. PubMed PMID: 36002557
10. Scigliano G, Scigliano GA. Methylene blue in covid-19. Medical hypotheses. 2021;146:110455. PubMed PMID: 33341032
11. Dabholkar N, Gorantla S, Dubey SK, et al. Repurposing methylene blue in the management of COVID-19: Mechanistic aspects and clinical investigations. Biomedicine & pharmacotherapy. 2021;142:112023. PubMed PMID: 34399199
12. Emadi E, Hamidi Alamdari D, Attaran D, et al. Application of methylene blue for the prevention and treatment of COVID-19: A narrative review. Iranian journal of basic medical sciences. 2024;27(7):780-792. PubMed PMID: 38800024
13. Böning D, Kuebler WM, Bloch W. The oxygen dissociation curve of blood in COVID-19. American journal of physiology. Lung cellular and molecular physiology. 2021;321(2):L349-L357. PubMed PMID: 33978488
14. Saha BK, Burns SL. The Story of Nitric Oxide, Sepsis and Methylene Blue: A Comprehensive Pathophysiologic Review. The American journal of the medical sciences. 2020;360(4):329-337. PubMed PMID: 32631574
15. Kirov MY, Evgenov OV, Evgenov NV, et al. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Critical care medicine. 2001;29(10):1860-7. PubMed PMID: 11588440
16. Ibarra-Estrada M, Kattan E, Aguilera-González P, et al. Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial. Critical care (London, England). 2023;27(1):110. PubMed PMID: 36915146
17. Fernando SM, Tran A, Soliman K, et al. Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis. Critical care explorations. 2024;6(7):e1110. PubMed PMID: 38904978
18. Kotani Y, Belletti A, D’Amico F, et al. Non-adrenergic vasopressors for vasodilatory shock or perioperative vasoplegia: a meta-analysis of randomized controlled trials. Critical care (London, England). 2024;28(1):439. PubMed PMID: 39736782
19. Cagno V, Medaglia C, Cerny A, et al. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. Scientific reports. 2021;11(1):14295. PubMed PMID: 34253743
20. Gendrot M, Andreani J, Duflot I, et al. Methylene blue inhibits replication of SARS-CoV-2 in vitro. International journal of antimicrobial agents. 2020;56(6):106202. PubMed PMID: 33075512
21. Gendrot M, Jardot P, Delandre O, et al. In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2. Journal of clinical medicine. 2021;10(14):3007. PubMed PMID: 34300178
22. Svyatchenko VA, Nikonov SD, Mayorov AP, et al. Antiviral photodynamic therapy: Inactivation and inhibition of SARS-CoV-2 in vitro using methylene blue and Radachlorin. Photodiagnosis and photodynamic therapy. 2021;33:102112. PubMed PMID: 33249118
23. Lobo CS, Rodrigues-Santos P, Pereira D, et al. Photodynamic disinfection of SARS-CoV-2 clinical samples using a methylene blue formulation. Photochemical & photobiological sciences. 2022;21(6):1101-1109. PubMed PMID: 35304729
24. Volle R, Murer L, Petkidis A, et al. Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids. Current research in microbial sciences. 2022;3:100158. PubMed PMID: 35935678
25. Bojadzic D, Alcazar O, Buchwald P. Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19. Frontiers in pharmacology. 2020;11:600372. PubMed PMID: 33519460
26. Kovalenko I, Kholina E, Fedorov V, et al. Interaction of Methylene Blue with Severe Acute Respiratory Syndrome Coronavirus 2 Envelope Revealed by Molecular Modeling. International journal of molecular sciences. 2023;24(21):15909. PubMed PMID: 37958892
27. Wei L, Ma Y, Ren Y, et al. Methylene Blue Has Strong Extracellular Virucidal Activity Against a SARS-CoV-2-Related Pangolin Coronavirus with No Intracellular or In Vivo Efficacy. Pathogens (Basel, Switzerland). 2024;13(11):958. PubMed PMID: 39599511
28. Tian ZG, Ji Y, Yan WJ, et al. Methylene blue protects against paraquat-induced acute lung injury in rats. International immunopharmacology. 2013;17(2):309-13. PubMed PMID: 23845394
29. Cassiano Silveira AP, Vento DA, Albuquerque AA, et al. Effects of methylene blue in acute lung injury induced by oleic acid in rats. Annals of translational medicine. 2016;4(1):8. PubMed PMID: 26855944
30. Wang L, Chen B, Lin B, et al. Methylene Blue Attenuates Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats. Mediators of inflammation. 2018;2018:2508620. PubMed PMID: 29713238
31. Ding F, Wang H, Qiao G, et al. Methylene blue mitigates lung injury in HCA rats by regulating macrophage pyroptosis via Nrf2/HO-1 and NLRP3 pathways. Biomolecules & biomedicine. 2025;25(9):2020-2034. PubMed PMID: 39957615
32. Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug safety. 2010;33(9):713-26. PubMed PMID: 20701405
33. Malakah MA, Baghlaf BA, Alsulami SE. Co-Occurring Hemolysis and Methemoglobinemia After COVID-19 Infection in Patient With G6PD Deficiency. Cureus. 2023;15(2):e35020. PubMed PMID: 36938163
34. Kashari OF, Alsamiri SA, Zabbani FM, et al. Occurrence of Methemoglobinemia due to COVID-19: A Case Report. Cureus. 2022;14(3):e23155. PubMed PMID: 35444908
35. Pushparajah Mak RS, Liebelt EL. Methylene Blue: An Antidote for Methemoglobinemia and Beyond. Pediatric emergency care. 2021;37(9):474-477. PubMed PMID: 34463662

Other Sources

1. Ghodke BA, Ghodke A, Mahadik V, Thorat P. Methylene blue treatment for moderate-to-severe cases of acute respiratory syndrome due to COVID-19 infection: clinical outcomes, a prospective study. MGM Journal of Medical Sciences. 2022;9(1):25-32. Published in a journal not indexed in PubMed. doi:10.4103/mgmj.mgmj_18_22
2. ClinicalTrials.gov. NCT04370288: The Clinical Trial of Application of Methylene Blue Vial for Treatment of Covid-19 Patients. First posted April 30, 2020; status unknown. clinicaltrials.gov
3. McMaster University Health Information Research Unit, COVID-19 Evidence Alerts. Rater comments on the Phase 2 trial, PubMed PMID 34019535 (archived copy, June 25, 2021; the service closed in 2025). web.archive.org
4. U.S. Food and Drug Administration (2011). FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. July 26, 2011 (archived copy). web.archive.org
5. U.S. Food and Drug Administration, Drugs@FDA. Methylene blue injection, 5 mg/mL, for intravenous use: prescribing information (NDA 204630), revised November 2023. accessdata.fda.gov

PubMed Topic Searches

1. PubMed: Methylene Blue and COVID-19, randomised trials
2. PubMed: Methylene Blue and acute respiratory distress syndrome
3. PubMed: Methylene Blue in septic shock, randomised trials
4. PubMed: Methylene Blue and SARS-CoV-2 in cells
5. PubMed: Methylene Blue and acute lung injury in rats

Back to Table of Contents

Connections

• Methylene Blue — the main page
• Methylene Blue — Benefits Deep Dive — the research hub
• Antiviral, Antimicrobial and Antiparasitic — blood-bank inactivation, malaria, light-activated uses
• Methylene Blue and Long COVID — symptoms after the infection
• Drug Interactions and Serotonin Syndrome — the boxed warning in detail
• Methemoglobinemia and Glucose-6-Phosphate Dehydrogenase Deficiency — the hemolysis risk
• Methylene Blue for Methemoglobinemia — the approved use
• Mitochondrial Mechanism and Bioenergetics — the electron-transport idea
• Drugs — the Pharmacology drugs index
• Acute Respiratory Distress Syndrome — the condition the trials studied
• Pneumonia — lung infection in general
• Respiratory Failure — when the lungs cannot keep oxygen up
• Sepsis — the setting of the septic shock trials
• How a Pulse Oximeter Reads Your Oxygen — why a blue dye can upset the reading
• Nicotine and COVID-19: The Research — another repurposing question from the pandemic

Back to Table of Contents